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Conserved Binding Sites

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...

Conserved Binding Sites

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...

Ligand Binding Sites

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...

Ligand Binding Sites

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...

Ligand Binding and Linkage

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...

Ligand Binding and Linkage

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...

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Related Experiment Video

Updated: Jul 8, 2026

A Protocol for Computer-Based Protein Structure and Function Prediction

A Protocol for Computer-Based Protein Structure and Function Prediction

Published on: November 3, 2011

A threading-based method (FINDSITE) for ligand-binding site prediction and functional annotation.

Michal Brylinski¹, Jeffrey Skolnick

¹Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, 250 14th Street NW, Atlanta, GA 30318, USA.

Proceedings of the National Academy of Sciences of the United States of America

|January 1, 2008

Summary

This summary is machine-generated.

FINDSITE accurately predicts ligand-binding sites and molecular function using protein models, even with structural inaccuracies. This method advances drug discovery by enabling analysis beyond experimentally solved protein structures.

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Last Updated: Jul 8, 2026

A Protocol for Computer-Based Protein Structure and Function Prediction

A Protocol for Computer-Based Protein Structure and Function Prediction

Published on: November 3, 2011

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

Published on: July 8, 2025

Area of Science:

Computational Biology
Structural Bioinformatics
Drug Discovery

Background:

Accurate detection of ligand-binding sites is crucial for protein function identification and drug discovery.
Current methods are limited to experimentally solved protein structures due to inaccuracies in predicted models.

Purpose of the Study:

To introduce FINDSITE, a novel method for predicting ligand-binding sites and annotating protein function.
To assess FINDSITE's performance using weakly homologous template structures and approximate protein models.

Main Methods:

FINDSITE utilizes binding-site similarity across weakly homologous templates identified via threading.
Ligand chemical properties are used to select relevant ligand templates associated with binding sites.
The method was evaluated on crystal structures and approximate protein models with varying sequence identities.

Main Results:

FINDSITE achieved 70.9% success rate and 76.0% ranking accuracy on crystal structures.
Performance was sustained on approximate models (<35% sequence identity), with 67.3% success and 75.5% ranking accuracy.
The method tolerates significant structural inaccuracies (up to 8-10 Å RMSD) in protein models.

Conclusions:

FINDSITE enables reliable ligand-binding site prediction and functional annotation from protein models, overcoming limitations of experimental structure requirements.
The method's robustness to structural inaccuracies and its ability to leverage weak homology make it valuable for large-scale protein analysis and drug discovery pipelines.